Diagnosis of histoplasmosis

Endemic mycoses can be challenging to diagnose and accurate interpretation of laboratory data is important to ensure the most appropriate treatment for the patients. Although the definitive diagnosis of histoplasmosis (HP), one of the most frequent endemic mycoses in the world, is achieved by direct diagnosis performed by micro and/or macroscopic observation of Histoplasma capsulatum (H. capsulatum), serologic evidence of this fungal infection is important since the isolation of the etiologic agents is time-consuming and insensitive. A variety of immunoassays have been used to detect specific antibodies to H. capsulatum. The most applied technique for antibody detection is immunodiffusion with sensitivity between 70 to 100% and specificity of 100%, depending on the clinical form. The complement fixation (CF) test, a methodology extensively used on the past, is less specific (60 to 90%). Detecting fungal antigens by immunoassays is valuable in immunocompromised individuals where such assays achieve positive predictive values of 96-98%. Most current tests in diagnostic laboratories still utilize unpurified antigenic complexes from either whole fungal cells or their culture filtrates. Emphasis has shifted, however, to clinical immunoassays using highly purified and well-characterized antigens including recombinant antigens. In this paper, we review the current conventional diagnostic tools, such as complement fixation and immunodiffusion, outline the development of novel diagnostic reagents and methods, and discuss their relative merits and disadvantages to the immunodiagnostic of this mycosis.